Associations between recorded loneliness and adverse mental health outcomes among patients receiving mental healthcare in South London: a retrospective cohort study.

PURPOSE: Loneliness disproportionately affects people with mental disorders, but associations with mental health outcomes in groups affected remain less well understood. METHOD: A cohort of patients receiving mental healthcare on 30th June 2012 was assembled from a large mental health records database covering a south London catchment area. Recorded loneliness within the preceding 2 years was extracted using natural language processing and outcomes were measured between 30th June 2012 until 30th December 2019, except for survival which applied a censoring point of 6th December 2020 according to data available at the time of extraction. The following mental healthcare outcomes: (i) time to first crisis episode; (ii) time to first emergency presentation; (iii) all-cause mortality; (iv) days active to service per year; and (v) face-to-face contacts per year. RESULTS: Loneliness was recorded in 4,483 (16.7%) patients in the study population and fully adjusted models showed associations with subsequent crisis episode (HR 1.17, 95% CI 1.07-1.29), emergency presentation (HR 1.30, 1.21-1.40), days active per year (IRR 1.04, 1.03-1.05), and face-to-face contacts per year (IRR 1.28, 1.27-1.30). Recorded loneliness in patients with substance misuse problems was particularly strongly associated with adverse outcomes, including risk of emergency presentation (HR 1.68, 1.29-2.18) and mortality (HR 1.29, 1.01-1.65). CONCLUSION: Patients receiving mental healthcare who are recorded as lonely have a higher risk of several adverse outcomes which may require a need for higher service input.

Rates of venous thromboembolism associated with acute psychiatric admission: A retrospective cohort study.

The present study aimed to identify rates of venous thromboembolism (VTE) amongst patients treated in inpatient mental health units using linked primary care and mental health care records. Patients resident in the London Borough of Lambeth admitted to mental health units in Southeast London between January 2008 and March 2019 were included, as well as a control group of patients being treated in the community for mental illness. The primary outcome measure was a diagnosis of VTE being recorded in GP records during or within 3 months of an admission to a mental health unit. For 7,198 psychiatric inpatient admissions, 11 episodes of VTE (1.5/1,000 admissions) were identified, with no VTE cases identified in 4,561 patients being treated in the community for mental illness during an equivalent window. This finding indicates that VTE rates following psychiatric inpatient admission might be similar to those following unselected acute medical admission. Larger scale studies are required to confirm the estimated incidence of VTE in patients with mental health conditions and the contribution of acute psychiatry hospitalisation to VTE risk.

Markers for the detection of Lewy body disease versus Alzheimer's disease in mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Mild cognitive impairment (MCI) may evolve into dementia. Early recognition of possible evolution to Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) is of importance, but actual diagnostic criteria have some limitations. In this systematic review and meta-analysis, we aimed to find the most accurate markers that can discriminate patients with DLB versus AD, in MCI stage. METHODS: We searched several databases up to 17 August 2023 including studies comparing markers that may distinguish DLB-MCI from AD-MCI. We reported data regarding sensitivity, specificity, and the area under the curves (AUCs) with their 95% confidence intervals (CIs). RESULTS: Among 2219 articles initially screened, eight case-control studies and one cohort study were included for a total of 832 outpatients with MCI. The accuracy of cerebrospinal fluid (CSF) markers was the highest among the markers considered (AUC > 0.90 for the CSF markers), with the AUC of CSF Aß42/Aß40 of 0.94. The accuracy for clinical symptom scales was very good (AUC = 0.93), as evaluated in three studies. Although limited to one study, the accuracy of FDG-PET (cingulate island sign ratio) was very good (AUC = 0.95) in discriminating DLB from AD in MCI, while the accuracy of SPECT markers and EEG frequencies was variable. CONCLUSIONS: Few studies have assessed the accuracy of biomarkers and clinical tools to distinguish DLB from AD at the MCI stage. While results are promising for CSF markers, FDG-PET and clinical symptoms scales, more studies, particularly with a prospective design, are needed to evaluate their accuracy and clinical usefulness. CLINICAL TRIAL REGISTRATION: Prospero (CRD42023422600).

A Blinded Evaluation of Brain Morphometry for Differential Diagnosis of Atypical Parkinsonism.

BACKGROUND: Advanced imaging techniques have been studied for differential diagnosis between PD, MSA, and PSP. OBJECTIVES: This study aims to validate the utility of individual voxel-based morphometry techniques for atypical parkinsonism in a blinded fashion. METHODS: Forty-eight healthy controls (HC) T1-WI were used to develop a referential dataset and fit a general linear model after segmentation into gray matter (GM) and white matter (WM) compartments. Segmented GM and WM with PD (n = 96), MSA (n = 18), and PSP (n = 20) were transformed into z-scores using the statistics of referential HC and individual voxel-based z-score maps were generated. An imaging diagnosis was assigned by two independent raters (trained and untrained) blinded to clinical information and final diagnosis. Furthermore, we developed an observer-independent index for ROI-based automated differentiation. RESULTS: The diagnostic performance using voxel-based z-score maps by rater 1 and rater 2 for MSA yielded sensitivities: 0.89, 0.94 (95% CI: 0.74-1.00, 0.84-1.00), specificities: 0.94, 0.80 (0.90-0.98, 0.73-0.87); for PSP, sensitivities: 0.85, 0.90 (0.69-1.00, 0.77-1.00), specificities: 0.98, 0.94 (0.96-1.00, 0.90-0.98). Interrater agreement was good for MSA (Cohen's kappa: 0.61), and excellent for PSP (0.84). Receiver operating characteristic analysis using the ROI-based new index showed an area under the curve (AUC): 0.89 (0.77-1.00) for MSA, and 0.99 (0.98-1.00) for PSP. CONCLUSIONS: These evaluations provide support for the utility of this imaging technique in the differential diagnosis of atypical parkinsonism demonstrating a remarkably high differentiation accuracy for PSP, suggesting potential use in clinical settings in the future.

Probiotics' Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014-2023 Clinical Trials.

Changes in the gut microbiome can affect cognitive and psychological functions via the microbiota-gut-brain (MGB) axis. Probiotic supplements are thought to have largely positive effects on mental health when taken in sufficient amounts; however, despite extensive research having been conducted, there is a lack of consistent findings on the effects of probiotics on anxiety and depression and the associated microbiome alterations. The aim of our study is to systematically review the most recent literature of the last 10 years in order to clarify whether probiotics could actually improve depression and anxiety symptoms. Our results indicate that the majority of the most recent literature suggests a beneficial role of probiotics in the treatment of depression and anxiety, despite the existence of a substantial number of less positive findings. Given probiotics' potential to offer novel, personalized treatment options for mood disorders, further, better targeted research in psychiatric populations is needed to address concerns about the exact mechanisms of probiotics, dosing, timing of treatment, and possible differences in outcomes depending on the severity of anxiety and depression.

BioPrint meets the AI age: development of artificial intelligence-based ADMET models for the drug-discovery platform SAFIRE.

Background: To prioritize compounds with a higher likelihood of success, artificial intelligence models can be used to predict absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of molecules quickly and efficiently. Methods: Models were trained with BioPrint database proprietary data along with public datasets to predict various ADMET end points for the SAFIRE platform. Results: SAFIRE models performed at or above 75% accuracy and 0.4 Matthew's correlation coefficient with validation sets. Training with both proprietary and public data improved model performance and expanded the chemical space on which the models were trained. The platform features scoring functionality to guide user decision-making. Conclusion: High-quality datasets along with chemical space considerations yielded ADMET models performing favorably with utility in the drug discovery process.

Estimating demand for potential disease-modifying therapies for Alzheimer's disease in the UK.

BACKGROUND: Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring. AIMS: To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK. METHOD: We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment. RESULTS: We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally. CONCLUSIONS: Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.

Long-term impact of the COVID-19 pandemic on the quality of life of people with dementia and their family carers.

INTRODUCTION: Few studies have longitudinally mapped quality of life (QoL) trajectories of newly diagnosed people with dementia and their carers, particularly during coronavirus disease-2019 (COVID-19). METHODS: In a UK cohort study, 261 newly diagnosed people with dementia and 206 family carers were assessed prior to the pandemic (July 2019-March 2020), followed up after the first lockdown (July-October 2020) and then again a year and 2 years later. Latent growth curve modelling examined the level and change of QoL over the four time-points using dementia-specific QoL measures (DEMQOL and C-DEMQOL). RESULTS: Despite variations in individual change scores, our results suggest that generally people with dementia maintained their QoL during the pandemic and experienced some increase towards the end of the period. This contrasted with carers who reported a general deterioration in their QoL over the same period. 'Confidence in future' and 'Feeling supported' were the only carer QoL subscales to show some recovery post-pandemic. DISCUSSION: It is positive that even during a period of global disruption, decline in QoL is not inevitable following the onset of dementia. However, it is of concern that carer QoL declined during this same period even after COVID-19 restrictions had been lifted. Carers play an invaluable role in the lives of people with dementia and wider society, and our findings suggest that, post-pandemic, they may require greater support to maintain their QoL.

First-in-human in-vivo depiction of paraganglioma metabolism by hyperpolarised 13C-magnetic resonance.

Phaeochromocytomas (PCC) and paragangliomas (PGL), cumulatively referred to as PPGLs, are neuroendocrine tumours arising from neural crest-derived cells in the sympathetic and parasympathetic nervous systems. Predicting future tumour behaviour and the likelihood of metastatic disease remains problematic as genotype-phenotype correlations are limited, the disease has variable penetrance and, to date, no reliable molecular, cellular or histological markers have emerged. Tumour metabolism quantification can be considered as a method to delineating tumour aggressiveness by utilising hyperpolarised 13 C-MR (HP-MR). The technique may provide an opportunity to non-invasively characterise disease behaviour. Here, we present the first instance of the analysis of PPGL metabolism via HP-MR in a single case.

A tool for safer prescribing in vulnerable adults: the continuing development of the Medichec app and website.

AIMS AND METHOD: Adverse effects are a common concern when prescribing and reviewing medication, particularly in vulnerable adults such as older people and those with intellectual disability. This paper describes the development of an app giving information on side-effects, called Medichec, and provides a description of the processes involved in its development and how drugs were rated for each side-effect. Medications with central anticholinergic action, dizziness, drowsiness, hyponatraemia, QTc prolongation, bleeding and constipation were identified using the British National Formulary (BNF) and frequency of occurrence of these effects was determined using the BNF, product information and electronic searches, including PubMed. RESULTS: Medications were rated using a traffic light system according to how commonly the adverse effect was known to occur or the severity of the effect. CLINICAL IMPLICATIONS: Medichec can facilitate access to side-effects information for multiple medications, aid clinical decision-making, optimise treatment and improve patient safety in vulnerable adults.

Code-Based Algorithms for Identifying Dementia in Electronic Health Records: Bridging the Gap Between Theory and Practice.

Code-based algorithms are crucial tools in the detection of dementia using electronic health record data, with broad applications in medical research and healthcare. Vassilaki et al.'s study explores the efficacy of code-based algorithms in dementia detection using electronic health record data, achieving approximately 70% sensitivity and positive predictive value. Despite the promising results, the algorithms fail to detect around 30% of dementia cases, highlighting challenges in distinguishing cognitive decline factors. The study emphasizes the need for algorithmic improvements and further exploration across diverse healthcare systems and populations, serving as a critical step toward bridging gaps in dementia care and understanding.

Association between late-life depression or depressive symptoms and stroke morbidity in elders: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: Whether late-life depression or depressive symptoms are a risk factor of future stroke in elders is important for prevention measures. A systematic review and meta-analysis were used to investigate the association between depression or depressive symptoms and risk of stroke in elders. METHODS: Embase, MEDLINE, PsychINFO, and Web of Science were searched for studies published from inception to January 6, 2023. Prospective cohort studies reporting quantitative estimates of the association between depression or depressive symptoms and stroke morbidity in participants aged over 60 years were included. Reviews, meta-analyses, case reports, retrospective, cross-sectional, and theoretical studies were excluded. Study screening and data extraction were conducted by two researchers independently. Random-effects meta-analysis was used to estimate pooled adjusted hazard ratios (HRs). Publication bias was evaluated via the symmetry of funnel plots and Egger tests. The Newcastle Ottawa Scale was used to assess the risk of bias. The quality of evidence of synthesis was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The primary outcome was any stroke, including non-fatal, fatal, ischemic and hemorrhagic sub-types. RESULTS: Seventeen studies of 57,761 patients in total were included in the meta-analysis. A positive association was found between depressive disorder or symptoms and stroke risk (HR: 1.39; 95% CI: 1.22-1.58; p < 0.001). CONCLUSIONS: Late-life depression or depressive symptoms are a significant risk factor for stroke in older people. Regular assessment and more effective management of associated comorbidities are recommended to reduce stroke risk.

Associations between air pollution and mental health service use in dementia: a retrospective cohort study.

BACKGROUND: Little is known about the role of air pollution in how people with dementia use mental health services. OBJECTIVE: We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia. METHODS: In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models. FINDINGS: In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO2: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11 to 1.45, p<0.001). Dose-response patterns between PM2.5 and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO2 levels were linked with poor functional status, but not cognitive function. CONCLUSIONS: Residential air pollution exposure is associated with increased CMHT usage among people with dementia. CLINICAL IMPLICATIONS: Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.

Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.

BACKGROUND: Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention. METHODS: Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure. RESULTS: AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class. CONCLUSIONS: This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.

Translational imaging of TSPO reveals pronounced innate inflammation in human and murine CD8 T cell-mediated limbic encephalitis.

Autoimmune limbic encephalitis (ALE) presents with new-onset mesial temporal lobe seizures, progressive memory disturbance, and other behavioral and cognitive changes. CD8 T cells are considered to play a key role in those cases where autoantibodies (ABs) target intracellular antigens or no ABs were found. Assessment of such patients presents a clinical challenge, and novel noninvasive imaging biomarkers are urgently needed. Here, we demonstrate that visualization of the translocator protein (TSPO) with [18F]DPA-714-PET-MRI reveals pronounced microglia activation and reactive gliosis in the hippocampus and amygdala of patients suspected with CD8 T cell ALE, which correlates with FLAIR-MRI and EEG alterations. Back-translation into a preclinical mouse model of neuronal antigen-specific CD8 T cell-mediated ALE allowed us to corroborate our preliminary clinical findings. These translational data underline the potential of [18F]DPA-714-PET-MRI as a clinical molecular imaging method for the direct assessment of innate immunity in CD8 T cell-mediated ALE.

Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity.

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1 -/- and Rgs1 +/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1 +/+ T cells outnumbered the co-transferred OT-I Rgs1- /- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1 -/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1 +/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1 -/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens.